2.1. CILIARY NEUROTROPHIC FACTOR
Ciliary neurotrophic factor (CNTF), as its name implies, is a protein that is specifically required for the survival of embryonic chick ciliary ganglion neurons in vitro Manthorpe et al., J. Neurochem. 34:69-75 (1980)!. CNTF has been cloned and synthesized in eukaryotic as well as bacterial expression systems, as described in International Application No. PCT/U.S. 90/05241, filed Sep. 14, 1990 which published as WO 91/04316 on Apr. 4, 1991 by Sendtner et al., incorporated by reference in its entirety herein.
Over the past decade, a number of biological effects have been ascribed to CNTF in addition to its ability to support the survival of ciliary ganglion neurons. CNTF is believed to induce the differentiation of bipotential glial progenitor cells in the perinatal rat optic nerve and brain Hughes et al., Nature 335:70-73 (1988)!. Furthermore, it has been observed to promote the survival of embryonic chick dorsal root ganglion sensory neurons Skaper and Varon, Brain Res. 389:39-46 (1986)!.
Several novel activities of CNTF have also been discovered, including its ability to support the survival and differentiation of motor neurons and hippocampal neurons, and to increase the rate of hippocampal astrocyte proliferation (International Application No. PCT/US 90/05241 which published as WO 91/04316 on Apr. 4, 1991, supra).